Chelated aryl

Chiral catalysts remain primary targets for immobilization by using similar methods. Since the steric arrangement of bulky aromatic groups of chiral ligands is the primary source of optical induction, most approaches use the chelate backbone of ligands for functionalization in order to minimize interference with the chelate (aryl) conformation. 

Although chelating aryl diphosphine ligands are effective for hydrogenating dehydroamino acids with high stereoselectivity, minor changes in the composition of the substrate can drastically lower the enantiomeric excess. The best results are obtained for the following structures ... 

Scheme 9.10 Preparation of the chelating aryl rhodium(I) complex 30 from 26 and 27a via the stable intermediate 28 by C—C bond activation...

Usually, iodides and bromides are used for the carbonylation, and chlorides are inert. I lowever, oxidative addition of aryl chlorides can be facilitated by use of bidcntatc phosphine, which forms a six-membered chelate structure and increa.scs (he electron density of Pd. For example, benzoate is prepared by the carbonylation of chlorobenzene using bis(diisopropylphosphino)propane (dippp) (456) as a ligand at 150 [308]. The use of tricyclohexylphosphine for the carbonylation of neat aryl chlorides in aqueous KOH under biphasic conditions is also recommended[309,310]. 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Addition of pyrazole to C—X double bonds is also common. Formaldehyde gives stable adducts (260) and (261) (69BSF2064), but in the addition to ketones, (262) is only observed at low temperatures (Section 4.04.1.3.3(i)). However, hexafluoroacetone forms a stable adduct (262 R = Cp3) that has been used as a chelating agent (Section 4.04.2.1.3(iv)). Addition of pyrazoles to aryl isocyanates affords (263) the addition is also reversible, but it requires high temperatures to dissociate the adduct (Section 4.04.1.5.1). 

The anions of 2-(arylsulfinylmethyl)oxazoles can be added to aldehydes to give 2-(l-aryl-sulfinyl-2-hydroxyalkyl)oxazoles which have been transformed into /1-hydroxy acids. With lithium bases, the enantioseleetivity could be increased to 50%. The use of a more chelating counter ion, such as magnesium, lowered the optical yields44. 

Lithium and zinc tert-butyl phenylmethyl sulfoxide (1) and A-phenyl imines 2, in which the substituent R is alkenyl or aryl, react at —78 °C over 2 hours with high anti diastereoselection (d.r. >98.5 1.5)6. Shorter reaction times result in poorer yields, due to incomplete reaction. In contrast, the reaction of the sulfoxide anion with benzaldehyde is complete after 5 seconds, but shows poor diastereoselection. When the substituent R1 or R2 of the imine 2 is aliphatic, the substrates exhibit poor chemical reactivity and diastereoselection. The high anti diastereoselection suggests that if a chelated cyclic transition state is involved (E configuration of the imine), then the boat transition state 4 is favored over its chair counterpart 5. 

Microwave-assisted Heck reaction of (hetero)aryl bromides with N,N-dimethyl-2-[(2-phenylvinyl)oxy]ethanamine, using Herrmann s palladacycle as a precatalyst, yielded the corresponding /3-(hetero)arylated Heck products in a good EjZ selectivity (Scheme 79) [90]. The a/yd-regioselectivity can be explained by the chelation control in the insertion step. This selectivity is better than 10/90 when no severe steric hindrance is introduced in the (hetero)aryl bromides. The process does not require an inert atmosphere. There is evidence that a Pd(0)/Pd(II)- and not Pd(II)/Pd(IV)-based catalytic cycle is involved. Similarly, other j6-amino-substituted vinyl ethers such as... 

Oxidative Heck arylation of enamides with arylboronic acids, using oxygen gas as a reoxidant for Pd(0) and 2,9-dimethyl-1,10-phenanthroline as a chelating regiocontrolling ligand, yielded a (= internally) arylated reaction product as the major compound with a very good a//3 selectivity [92]. Microwave irradiation with prepressurized sealed vials proved useful in reducing the reaction time (Scheme 82). 

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